Animal experiment:

To induce a systemic S. pneumoniae infection, male ICR mice (weight, 18 to 20 g) are inoculated intraperitoneally with 1 of 4 PRSP isolates (DR9, DR10, DR11, or DR14) suspended in 10% mucin. The suspension contained sufficient bacteria to kill 100% of untreated control mice. At 1 h postinfection, mice receives a single dose of either tedizolid phosphate or linezolid, and survival is assessed daily for 7 days postinfection. Treatments are delivered both orally and intravenously at each of four doses (40 mg/kg of body weight, 13.33 mg/kg, 4.44 mg/kg, and 1.48 mg/kg), with 8 mice per group defined by dose, delivery method, and infecting strain. The 50% effective dose (ED50), i.e., the dose allowing survival of 50% of the infected mice, is calculated for each delivery route using probit analysis.

Tedizolid phosphate is a prodrug form of tedizolid, an antibiotic with activity against Gram-positive bacteria. Tedizolid phosphate is rapidly converted by non-specific phosphatases to tedizolid, which inhibits the growth of S. aureus, S. epidermidis, E. faecalis, E. faecium, S. pneumoniae, and S. pyogenes (MICs = 0.25-1 μg/ml). In vivo, tedizolid phosphate (15 mg/kg) reduces vegetation titer in a rabbit model of aortic valve endocarditis caused by methicillin-resistant S. aureus (MRSA). It also reduces densities of methicillin-susceptible S. aureus and MRSA infection in a mouse model of catheter-related biofilm infection and increases survival in a rabbit model of MRSA necrotizing pneumonia.